. Cationic liposomes are currently the most promising potential delivery system for expression of DNA in eukaryotic cells. They have many desirable characteristics for use in the new field of gene therapy, but their efficiency is still less than ideal. In the proposed research the structure-activity relationships between a series of novel polycationic lipids and their transfection efficiencies in delivering nucleic acids into mammalian cells will be studied. The thrust of the proposed research is the synthesis of new lipids whose nucleic acid transfection efficiencies are several fold greater than those of currently commercially available lipids with minimal or no toxicity. These lipids possess chemical functionalities as well as stereochemical characteristics which have not been previously explored in the field of liposome research. These lipids will be tested in commonly used cell lines as well as in primary and postmitotic cells. Efficiencies will be determined using a beta-Gal or green fluorescent protein assay. Some of these lipids might have unique properties applicable not only to DNA transfection and gene therapy, but also in the multibillion dollar detergent and cosmetics industry.